Thanks to a recent study at retina centers in Japan and New York City, the mysterious yet multitasking choroid has revealed one of its secrets: It is the only significant predictor for visual acuity in highly myopic eyes without macular pathology.1

“We’ve known the choroid is vital to visual function—delivering copious amounts of oxygen and metabolites—and that its thickness decreases with age and in myopia,” said coauthor Richard F. Spaide, MD, in private practice with the Vitreous-Retina-Macula Consultants of New York. “But we haven’t understood everything it is doing.”

In the absence of macular pathology, the mechanism for visual loss in high myopia has not been clear. Previously, researchers proposed retinal stretching as a possible cause, but no study had confirmed this theory by measuring retinal or choroidal thickness with optical coherence tomography (OCT).

However, with the advent of enhanced depth imaging OCT, it became possible in this study to image deeper structures in the eye, including the central fovea, the outer retinal hyporeflective layer, and the inner segment to retinal pigment epithelium (RPE) aggregate, as well as subfoveal choroidal thickness.

In both cohorts of this study, subfoveal choroidal thickness—which is normally about 220 µm—was inversely correlated with age and myopic refractive error.

In the Japanese group, mean subfoveal choroidal thickness was 172.9 µm (110 eyes of 61 patients aged 46.8 ± 14.7 years, with a mean refractive error of –9.2 D and a mean axial length of 27 mm). In the New York group, mean subfoveal choroidal thickness was 113.3 µm (23 eyes of 25 patients aged 57 ± 18.1 years, with a mean refractive error of –10.9 D). Axial length was not measured in the New York group.

After correcting for age and refractive status, said Dr. Spaide, the authors found no significant difference between the two groups. “That implies—as far as the choroid is concerned—that high myopia is high myopia, and these changes may be independent of race.”

Although inner segment to RPE aggregate thickness in the Japanese cohort also was negatively correlated with visual acuity, this correlation was not notable in either the New York or the pooled data, suggesting that retinal features are not significantly linked with visual acuity in high myopes.

“This was not expected,” said Dr. Spaide, explaining that both a thinning choroid and decreasing vision had made the retina a likely suspect. “We knew the choroid would be thinner, but we didn’t know the visual acuity would be changed in a proportionate manner.” The authors suggest that a very thin choroid may deliver decreased amounts of oxygen and nutrients to the outer retina, which might affect signal generation by the photoreceptors or lead to loss of overlying photoreceptors.

Given the growing myopia epidemic—largely tied to near work in childhood and lack of outdoor activities—these findings may have widespread implications, said Dr. Spaide.

“If we can maintain the vitality of the choroid, we may beat the pathologic effects of myopia without necessarily having to do anything with refractive error,” he said.

—Annie Stuart

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1 Nishida Y et al. Retina. 2012;32(7):1229-1236.

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Dr. Spaide receives royalty payments from Topcon Medical Systems.

Cataract Report

Study Finds That Cataract Surgery Review Can Wait

Typically, doctors examine patients on the first or second day following phacoemulsification cataract surgery to detect treatable complications. But a team of Greek researchers has concluded that if the surgery goes well and the patient has an uncomplicated history, you can wait longer than this.1

The team, headed by Irini P. Chatziralli, MD, randomized 291 patients who underwent uneventful cataract surgery into two groups: next-day review (NDR) and no next-day review (NNDR). NDR patients stayed in the hospital overnight and were examined the following morning. NNDR patients were discharged within four hours. The same surgeon performed all surgeries at a rural public hospital in Veroia, Greece.

All patients returned on day 14 for slit-lamp exam, tonometry, and funduscopy. The exam was repeated on day 28, when BCVA was also measured.

Outcomes were similar in both groups. In the NDR group, 8 (5.5 percent) patients developed a postoperative complication, compared with 9 (6.2 percent) in the NNDR group. The most frequent complications included elevated IOP, allergic reaction to postoperative medications, corneal abrasion, punctate epitheliopathy, iris prolapse, and postoperative hyphema.

There was also no difference between the groups for the other measured outcomes: rate of patients seeking unscheduled medical consultation up to day 14 following surgery; presence of inflammation, such as corneal edema or conjunctival hyperemia on day 28; and BCVA on day 28.

All complications in the NDR group were detected on next-day review, except for allergy to topical medication, which prompted later unscheduled visits. In the NNDR group, all complications became evident on or before day 14.

Allergy to medication is not vision threatening and can be predicted based on a thorough medical history, the authors said. And the most frequent complication—elevated IOP—is transient, peaking between three and six hours postoperatively. It is more common in the subset of patients with coexisting glaucoma and can be prevented with prophylactic topical pressure-lowering medications.

The literature regarding the necessity of day 1 review is conflicted, so before this study, Dr. Chatziralli did what most Greek doctors do—examined all phacoemulsification cataract surgery patients the following day. Now she eliminates the first postoperative day review unless the surgery was complicated or the patient has glaucoma, previous uveitis, or other atypical history. “Our study changed my practice,” she said.

Providing another perspective, Bonnie An Henderson, MD, in private practice at Ophthalmic Consultants of Boston, said, “Although the authors report that the complication rate and final outcomes by day 28 are similar between the two groups, this single small study should not be taken as justification for forgoing the day 1 postoperative visit after cataract surgery. Surgeons should use their best judgment in deciding the appropriate follow-up schedule for each patient.”

If a patient presents with orbital inflammation and you don’t know the cause, ask if he or she has been to the dentist recently. That’s the advice of a team of researchers who propose that some cases of acute orbital inflammation may represent an autoimmune response triggered by dental work.

The team reported three cases of noninfectious orbital inflammation occurring soon after dental work.1 Two cases occurred following routine dental cleaning; one followed tooth extraction.

The first case presented in 2008, in a patient who mentioned having had her teeth cleaned one week before onset of inflammation. “We found this fact to be unusual, yet we did not make much of it at the time,” said M. Reza Vagefi, MD, a coauthor of the report and assistant professor of ophthalmology, University of California, San Francisco.

Orbital inflammation represents only about 6 percent of orbital disease, so more than a year passed before a similar case appeared. “From that point forward, we began to routinely ask patients with orbital inflammation if they had had recent dental work,” said Dr. Vagefi.

“Autoimmunity after systemic infection is not a new concept,” he continued. Cases of orbital and intraocular inflammation have been documented after other types of infections, but often the cause is not identified.

In fact, the cause in the three cases has not been established. “We are hypothesizing a connection based on an observation,” Dr. Vagefi said. The hypothesis involves a complex cascade of events, which he hopes to explore in an animal model, by inducing orbital inflammation from oral bacterial flora.

In the meantime, he prescribes steroids as a first-line agent in cases of idiopathic orbital inflammation in which there’s no infection. The three cases responded to steroids.

It’s reasonable to ask patients with idiopathic orbital inflammation about recent dental work, he added. “I think we will probably identify more cases after dental manipulation because, hopefully, now we are more likely to ask the question and make the connection.”

Although acetazolamide is a first-line medical therapy for idiopathic intracranial hypertension (IIH), ophthalmologists have been concerned about using it in pregnant patients due to teratogenic effects reported in experiments with rodents and rabbits, which produced limb deformities. But a retrospective study that surveyed IIH patients and their physicians showed reassuring pediatric outcomes, presenting a more optimistic picture.1

The researchers collected data on pregnancy and offspring outcomes in 101 women with IIH (158 pregnancies). In 63 of the pregnancies (50 in the first trimester), the woman was treated with acetazolamide for IIH. Risk of spontaneous abortion was similar to the control group (women who did not receive the drug during the first trimester). No major complication was identified in any of the children of the treated women.

The researchers concluded that there is a lack of convincing evidence of adverse effects from acetazolamide use in human pregnancy, even when the drug is used during the first trimester.

Based on the study results, neuro-ophthalmologist Julie Falardeau, MD, a coauthor of the study and assistant professor of ophthalmology at the Oregon Health & Science University in Portland, said, “I believe it is reasonable to use acetazolamide during the first trimester in pregnant patients with IIH who are significantly symptomatic and at potential risk of vision loss. The risk-benefit ratio would favor the treatment for such a patient.

“Still,” Dr. Falardeau said, “it should be used with caution and justification. Negative data do not exclude the teratogenic possibility. Appropriate counseling should take place.”

The pressures maintained by the eye’s production and drainage of aqueous have long been known to fluctuate according to a range of external factors, such as the time of day, sleep-wake cycles, changes in systemic blood pressure, even an individual’s caffeine consumption. But researchers at the Mayo Clinic in Rochester, Minn., have honed those fluctuations even further—down to specific anatomic positions of the neck and torso.1

Mean IOP was lowest when the volunteers were upright with neutral neck position (14.8 ± 2.0 mmHg), significantly higher in neck extension (16.4 ± 2.7 mmHg), and higher yet in neck flexion (19.8 ± 3.8 mmHg). IOP was also elevated when the volunteers were checked in reclining positions. Pressure in the supine position was 17.3 ± 2.9 mmHg. Pressures in the decubitus positions were greater in the lower eye than the fellow eye—the right eye in right lateral decubitus position was 18.8 ± 2.9 vs. 17.7 ± 3.1 mmHg in the left eye; the left eye in left lateral decubitus position was 18.3 ± 2.8 mmHg vs. 17.6 ± 2.6 mmHg in the right.

Dr. Sit noted that no firm conclusions can yet be made for clinical care. One intriguing possibility, for example, might suggest itself: Could preemptive ocular antihypertensives benefit patients who must remain in bed for long periods, such as during high-risk pregnancies or recovery from trauma or orthopedic surgery? “That’s a million-dollar question—but we just don’t know yet the clinical relevance of IOP elevation in these various body postures.”

Not even the mechanism responsible for pressure elevations is known for certain, he said. “It’s probably related to gravity in the recumbent positions, but for changes in neck position I would attribute pressure elevations more to the slight but real occlusion of venous return that occurs when we flex or extend our necks.” Dr. Sit added that the simple human instinct to turn over periodically during sleep not only prevents pressure on bony prominences, like the heels and the sacrum, but may also, theoretically, help relieve the lower eye from pressure increases in people who sleep mostly on one side.

—Denny Smith

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1 Malihi M, Sit A. Ophthalmology. 2012;119(5):987-991.

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Dr. Sit is a consultant to Acu-MEMS, Alcon, Allergan, Glaukos, and Sensimed. He receives research support from Glaukos.

Retina Report

Poppers Maculopathy Found in the United Kingdom

A patient with puzzling vitelliform foveal lesions might be showing this retinal damage because of recreational use of alkyl nitrite “poppers,” British ophthalmologists warned recently.

“Ophthalmologists should ask patients with unexplained foveal yellow spots or outer lamellar macular changes on OCT imaging about inhalation of poppers,” the authors wrote in their case report.1

Although several similar cases have been reported in France since 2010,2-4 this was the first published report from the United Kingdom of “poppers maculopathy,” said Simon P. Kelly, FRCSEd, FRCOphth, FEBO, a consultant ophthalmologist at the Royal Bolton Hospital based in Lancashire, England.

Dr. Kelly said the group also has a second paper in press at Eye about several more British patients with poppers maculopathy.

“Quite a lot of people have actually taken poppers. They are not uncommon in the gay and nightclubbing and youth culture,” he said. “When we told patients that poppers could be harming their vision, they were quite shocked. They thought using poppers was harmless.”

Named for the small glass vials that 1960s cardiovascular patients “popped” to inhale a prescribed dose of amyl nitrite, poppers quickly became popular with recreational users seeking to enhance sexual experiences. Today, users buy small bottles of nitrite liquids online or at sex shops. To stay within the law, poppers products are labeled for other uses, such as room odorizer.

The patient in Dr. Kelly’s case report was a 53-year-old man who admitted to inhaling isopropyl nitrite every day for the previous 18 months. His best-corrected binocular visual acuity had declined to 6/18 (20/60) from 6/5 (20/16) two years earlier.

“Poppers have been around a long time,” Dr. Kelly said. “The question is: Why has this problem not been prevalent for decades?”

One possible answer might be the switch from isobutyl nitrite to isopropyl nitrite in British poppers preparations a few years ago, Dr. Kelly said. The change was prompted by tighter regulation of isobutyl nitrite in the United Kingdom, he said.

Some nitrite compounds are more powerful vasodilators than others, but their relative potency, and the biologic reasons for the differences, are poorly understood, said Frank Romanelli, PharmD, MPH, BCPS, a University of Kentucky professor of pharmacy practice who has studied nitrite abuse.5

“You never know what switching out one entity for another will do to absorption, penetration, and distribution of the drug,” Dr. Romanelli said. “So changing to the isopropyl form, for instance, might alter the fat absorption of the drug and change the way it is distributed in the body.”

Richard F. Spaide, MD, a retina subspecialist in New York City, noted that a hint as to how poppers might cause maculopathy comes from the location of the maculopathy. SD-OCT in Dr. Kelly’s patient showed the damage was along the photoreceptor inner segment/outer segment junction, confined to the area below the foveal pit in both eyes.

Mitochondria in photoreceptors are sensitive to higher doses of nitrites, Dr. Spaide said. “The photoreceptors have the highest density of mitochondria of any cell in the body,” he added. “It is possible that the alterations we see in the fovea by ophthalmoscopy or OCT are the result of mitochondrial damage.”

—Linda Roach

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1 Davies AJ et al. Eye. 2012;26(6):888.

2 Vignal-Clermont C et al. N Engl J Med. 2010;363(16):1583-1585.

3 Audo I et al. Arch Ophthalmol. 2011;129(6):703-708.

4 Schulze-Döbold C et al. Ann Intern Med. 2012;156(9):670-672.

5 Romanelli F et al. Pharmacotherapy. 2004;24(1):69-78.

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Dr. Kelly reports no financial interests. Dr. Spaide is a consultant to Topcon and ThromboGenics.